Solutions of the hydrochloride were licitly used on man as a short-acting analgesic and for general anesthesia under the trade name Sernyl (Chen
et al, 1959; McCarthy, 1972). Because of post-operative side effects, however, the regulation was later changed under the New Drug Application to permit the manufacture by Philips Roxane of a solution under the trade name Sernylan (Gouge, 1972), serving as an analgesic for monkeys and other primates. Recent United States legislation (Comprehensive Drug Abuse Prevention, 1970) classified PCP together with barbiturates and lysergide.

PCP was detected by extraction with an organic solvent from an aqueous solution; concentrations of 1:1,000 give colour reactions with gold bromide and with potassium permanganate. It is quantitatively determined by thin layer or by gas chromatography with mass spectrography (Clarke, 1959: Hammar
et al, 1969; Finkle
et al, 1971; Law
et al, 1971; Lindgren
et al, 1969; Schnoll
et al, 1971). As mentioned before, PCP is licitly produced in the form of a solution which is being sold for veterinary use (Long
et al, 1969).

According to seizure reports illicit products containing PCP are sold only in a solid state as tablets or capsules. Apparently the first illicit powder produced by some (unknown) foreign manufacturer was smuggled into the San Francisco area under the nickname "PeaCe Pill" or "THC" about the year 1966. Sprinkled on dried parsley or low-grade marihuana for smoking, it was called "Angel Dust" (Davis
et al, 1968; Greene, 1971; Lindgren
et al, 1969; Lofholm, 1968; Meyers
et al, 1967; Reed et al, 1972). Spreading among the hippies and other users of hallucinogenic drugs along the West Coast, it rapidly crossed the American continent to appear in New York City as "Hog" (Davis
et al, 1968; Greene, 1971; Lindgren
et al, 1969). Many clandestine laboratories began to produce an impure powder in which the impurities are more toxic than PCP itself (Lampe, 1971), leading to hallucinations, coma and death.

PCP has become the primary constituent of "street drugs", either as the only ingredient of a capsule or in admixture with amphetamine, cocaine, mescaline, THC and LSD, to name a few. Physicians have been warned that in cases necessitating emergency treatment other than the alleged substances may be involved (Anon, 1970; Anon, 1970; Anon, 1971; Anon, 1971; Anon, 1971; Anon, 1971; Medical Letter, 1971). PCP was detected in 184 of 237 samples of "street drugs" submitted for identification to the Department of Chemistry, University of Kansas, between August 1970 and January 1972:(2 of the 57 samples sold as LSD did in fact contain LSD; 17 of the 45 samples sold as mescaline; 2 of the 16 samples sold as psilocybin; one of the samples alleged to be MDA; one of the 5 samples sold as "Hawaian Woodrose"; 2 of the 8 declared to be psychedelics; 10 of the 11 samples sold as THC, and 2 of the 34 samples undesignated (Hart
et al, 1972).

Similarly, PCP was detected in 195 samples of "street drugs" during a period of two months: 16 were sold as LSD; 5 of the 10 samples as THC; 5 as psilocybin, and some as mescaline (Pharm. Chem. Labs., 1973). In Philadelphia it was found that PCP was contained in 8 of the 20 samples sold as mescaline, and that other combinations contained cocaine, LSD or amphetamine (Schnoll
et al., 1972; Schnoll
et al 1971).

Wide species differences were observed in animal studies; mice and rats developed excitation followed by depression, whereas other species showed only depression. Great variations in dosage were required to produce analgesia and anesthesia (Chen
et al, 1959). As a local anesthetic PCP was twice as effective as procaine, half as potent as cocaine. Toxic doses produced bradycardia and clonic convulsions, followed by death from respiratory failure. Resistance to electric shock in 200-400 gm trained rats increased as doses were increased from 2 mg/kg to 8 mg/kg subcutaneously. Chlorpromazine blocked the response to PCP (Domino
et al, 1960). These observations were confirmed and extended by other investigators (Carr, 1959; Laurence, 1966; Rice, 1972; Usdin
et al, 1972), who in their studies on animals and human subjects used it as an analgesic and a general anesthetic. Oral administration to caged wild birds showed LD
50 values ranging from 5.6 mg/kg for bobtail grackles to 75 mg/kg for mallard ducks, 133 mg/kg for sparrows and ring-neck pheasants to 237 mg/kg for starlings and pigeons (Schafer, 1972).

For metabolic studies a lot of tagged PCP was prepared in which C 14 was placed in the phenyl ring, and tritium in the 3.4-positions in the piperidine ring. Monkeys rapidly metabolized the tagged material to both mono- and dihydroxy piperidine derivatives, which were then conjugated and excreted in the urine. Other species of animals varied in metabolic pathways; cats excreted PCP unchanged. Human subjects excreted chiefly the mono-hydroxy-piperidine complex. The metabolites were weaker in action, and not considered to contribute to the pharmacological response evoked by PCP (Ober et al, 1963).

Range of hydroxy-derivative excreted:

Species

Dihydroxy-per cent

Mono-hydroxy-per cent

Humans

0

29-68

Mice

25-50

29-68

Rats

75

5-14

Pigeons

75

5-14

Cats

0

5-14

Dogs

0

85-100

Monkeys

25-50

29-68

Sheep

25-50

29-68

Cows

0

85-100

Horses

0

85-100

In another more detailed study on urinary excretion (Hucker, 1970) marked species differences were obtained in urinary excretion of PCP and the hydroxypiperidine derivatives, as shown in the table on p. 10. The unchanged PCP was more active and more toxic than the hydroxypiperidine metabolites.

Gastrointestinal tract: Nausea in 50 of 55 mental patients after intravenous injections of 0.01 to 0.10 mg/kg; occasional nausea and vomiting in half the children receiving PCP (Lister, 1966); and in 12 normal volunteers after injection of 0.075 mg/kg to 0.10 mg/ kg (Davies
et al, 1960). Prolonged studies in 15 Nigerian hospitals where PCP was used as a general anesthetic revealed that post-operative nausea and vomiting occurred in 5 out of 500 patients (Gool
et al, 1964), and in 1 out of 51 patients after administration of 0.06 mg/kg of PCP intravenously (Greifenstein
et al, 1958). Excessive salivation has also been reported (Cutting, 1967).

Oral administration of 7.5 mg of PCP to 18 subjects led to increased visual acuity, touch threshold, position and sensory thresholds for 2 hours, which then returned to the pre-administration values (Morganstern
et al, 1962). In another study oral doses of 10 mg produced mental confusion, delirium, hallucinations, apathy and a feeling of isolation in a group under observation (Domino, 1964). An oral dose of 10 mg of PCP given 8 healthy college graduates over 21 years of age produced only slight changes while in a test chamber; however, on emerging, distorted perception and prolonged reaction time were noted; proprioceptive senses were especially depressed, by comparison no effect developed in a double-blind study after administration of a placebo (Pollard
et al, 1960).

Patients: Following intravenous injections of 0.01 to 0.10 mg/kg schizophrenic-like symptoms increased as did the reaction time; it was concluded that "side effects preclude clinical use in humans" (Ban
et al, 1961). In 735 patients observed in 15 Nigerian hospitals intravenously administered doses from 0.275 mg/kg to 0.44 mg/kg produced anesthesia of short duration, averaging 25 minutes; the principal disadvantage reported was postoperative confusion and hallucinations. Even though 77 per cent of the entire group showed no complications, the authors concluded that "routine use for adults is unacceptable" (Gool
et al, 1964). In another study on 51 patients 0.25 mg/kg caused mild excitement in 12 of them; severe excitement in 3, and disorientation in 13 patients for 3 to 18 hours. After trials on 64 patients, 10 developed unmanageable severe maniac behaviour, 3 became violent, and 1 patient was semiconscious for 10 days. In 6 surgical patients, EEG showed slow
t waves after administration of 2 to 3 mg intravenously, and after administration of 7 to 10 mg, slowed temporal and parietal region responses. The authors concluded that PCP was "worth further study" (Greifenstein
et al, 1958). Doses of 10 mg administered postoperatively produced excellent relief from pain and muscle disturbances; 20 mg prolonged hallucinations and psychoses, especially in young adults, and excitement lasting up to 12 hours; so the authors concluded: "inadvisable as sole agent for anesthesia" (Johnstone
et al, 1959). After doses of 2.0 to 2.5 mg/kg severe reactions developed, such as loss of speech for 15 minutes, followed by excessive talking: irritability lasting for 1 to 2 hours, acting as an "interoceptive sensory blocking agent" (Lambert, 1964).

Oral doses of 0.25 mg administered three times daily for several weeks, then increased to 0.5 mg three times daily, improved the state of health of 25 of 32 psychoneurotics, but only 3 became asymptomatic; 29 were maintained at the larger dose level without adverse side effects: the authors conclude that PCP was "only moderately effective" (Bodi
et al, 1959). Patients became calm, with a feeling of "utter nothingness" during treatment (Cohen
et al, 1960; 1962).

Successful anesthesia developed in 93 of the 100 patients, but 11 showed postoperative disturbances, so PCP was considered as "clinically unacceptable" (Helrich
et al, 1964). Another investigator (Lister, 1966) listed a high incidence of toxic effects; overstimulation of the central nervous system, marked irritation, unpleasant nausea, and salivation in half of the patients, so that PCP was "withdrawn from clinical use". Analgesia produced by PCP was adequate in 78 per cent of children treated for burns, but half developed severe crying spells and hallucinations (Muir
et al, 1961). In other studies apathy and feelings of isolation, especially characteristic reaction of schizophrenic patients, were reported (Freedman
et al, 1967; Kaufman
et al, 1969).

At a conference on environmental mutagens it was reported that PCP has been found to be teratogenic; "Users of phencyclidine had increased rates of fetal loss, decreased fertility, extensive chromosome breakage, and increased presence of a small chromosome that resembled the Philadelphia chromosome. Their offspring had an abnormally large incidence of spinal defects, limb reduction anomalies, triploidy, and trisomy" (Walker, 1974).

The range from the effective to the toxic dose is narrow (Clarke, 1959). PCP is relatively more toxic to the aged (Cooper, 1968; Medical Letter, 1970). Missynthesis of PCP produces byproducts that are very toxic, causing abdominal cramps, bloody emesis, coma and respiratory death (Lampe, 1971). Two women "procured" and ate a chicken which had been treated experimentally with PCP; both developed marked mental symptoms but survived (Poison Information Service, 1967). No deaths from ingestion of PCP were reported until 1971 (Marshman
et al, 1969; 1971); a fatal case appeared in the literature the next year (Reed
et al, 1972). A 19-year old man was found dead in his room: his clothing contained 10 packets of PCP, each assaying between 2.0 and 3.5 mg of PCP. Visceral congestion and posterior lobe pneumonia were found at autopsy. Analyses confirmed the presence of 70 mg of PCP in the gastric contents; the urine contained 3.8 mg, the liver 0.09 mg, the lungs 0.04 mg, the blood 0.03 mg, the brain and the kidney 0.01 mg per cent. No other drug was detected in the stomach contents, urine or liver. In another poison case, another 19-year old male was hospitalized after taking 50 tablets, each 110 mg containing 97 per cent pure PCP. The blood and urine values on admission were within normal limits; blood pressure 200/80. Treated with "benign neglect" for several days, the blood pressure fell to 120/80. Then treatment with 100 mg of chlorpromazine four times daily, and hydrocortisone sodium succinate daily over the next 10 days led to recovery. The patient showed aggressive hostility during treatment (Stein, 1973). Similar reports have been published on two children by Liden
et al, 1973, and by Rainey
et al, 1974.

Haloperidol has been suggested to modify PCP actions and effects (Gool
et al, 1964; Helrich, 1964). The administration of succinates has been advocated as antidotes for both the central and peripheral effects of PCP; one patient rapidly developed mental clearing following oral administration (Gershon
et al, 1960). However another study (Neubauer
et al, 1966) failed to confirm the value of the succinates. A warning has been issued against the use of atropine or the belladonna alkaloids as definitely contraindicated (Taylor
et al, 1970). No other reports of antidotal therapy have been found in a search of the literature.

Phencyclidine (PCP) was introduced in 1960 as an analgesic and general anesthetic for man, but too many severe adverse effects developed, including hallucinations, manic depressive and schizophrinic-like symptoms. A
solution of the hydrochloride has been approved for anesthesia of monkeys and other primates. PCP
powder from clandestine sources has become a primary constituent of the "street drugs" illegally used by narcotic addicts, displacing heroin to a large extent. It may be found in dilute powder form alone, or admixed with LSD, amphetamine, cocaine, tetrahydrocannabinol (THC), mescaline or other drugs. Users of "street drugs" have experienced violent mental disturbances. Antidotes are still to be developed; one death has been reported to date. PCP is properly classed as a "dangerous drug".